利尿劑Hydrochlorothiazide 製劑之溶離曲線比對試驗   全文下載

A Comparative Study on the Dissolution Profiles of Commercial Hydrochlorothiazide Tablets

本研究旨在探討市售Hydrochlorothiazide單方錠劑與原開發廠美國默沙東藥廠（Merck Sharp & Dohme, N.J., U.S.A. ）之Dichlotride錠劑對照品溶離曲線之相似性，每一檢體均分別以水、0.1N HCl及pH 7.4磷酸緩衝液為溶媒，採用USP裝置I （Rotating Basket Apparatus），轉速100 rpm，測定10、20、30、45、60及90分鐘各時間點之溶離量，以繪製溶離曲線；並依照FDA所提SUPAC之f2 因子，與對照品比較其相似性。十六件檢體之溶離曲線與對照品比對結果，於三種溶媒之溶離曲線均與對照品相似者有五件（相似比率約31.3%），於水及0.1N HCl二溶媒中具相似性但於pH 7.4磷酸緩衝液不相似者有三件（約18.8%），而各只於單一溶媒，即0.1N HCl 或pH 7.4磷酸緩衝液，具相似性者各一件（各約6.3%），其餘六件（37.5%）於三種溶媒之溶離曲線均與對照品不相似。綜合16件檢體與原廠對照品之溶離曲線的相似性，分別為水中溶離相似者八件（50%），0.1N HCl溶離相似者九件（56.3%）及pH 7.4磷酸緩衝液溶離相似者六件（37.5%）。"

Dissolution profiles (DPs) of Dichlotride tablet containing hydrochlorothiazide, supplied by Merck Sharp & Dohme, N. J., U.S.A. and used as the reference formulation in this study, were compared with those obtained from sixteen commercial tablets. Dissolution tests were performed by employing a USP XXIII apparatus-I (Basket type) at 100 rpm. Pure water, 0.1N HCl and pH 7.4 buffer were used as the studied media. Released percentages of the active ingredient were measured at 10, 20, 30, 45, 60 and 90 minutes, respectively. The factor f2 of the FDA’s SUPAC Guide was applied to the qualitative determination of ‘similarity’ between pairs of dissolution profiles of Dichlotride and those of each investigated formulations. Results indicated that 5 out of 16 tested samples (ca. 31.3%) were suited to Dichlotride in all of three media. In addition, three other samples (ca. 18.8% each) were similar to Dichlotride in both water and 0.1N HCl. Two tested formulations gave similar in-vitro release profiles to those of Dichlotride only in corresponding pure water or the pH 7.4 buffer solution (ca. 6.3% each), in other words, different in both of the other two media. The last six samples showed completely different profiles compared with that of Dichlotride no matter what medium was used. In summary, the number of tested samples showing similar DPs as Dichlotride in individual media were as follows: 8 in water (50%); 9 in 0.1N HCl (ca. 56.3%); and 6 in pH 7.4 buffer solution (37.5%). 本研究旨在探討市售Hydrochlorothiazide單方錠劑與原開發廠美國默沙東藥廠（Merck Sharp & Dohme, N.J., U.S.A. ）之Dichlotride錠劑對照品溶離曲線之相似性，每一檢體均分別以水、0.1N HCl及pH 7.4磷酸緩衝液為溶媒，採用USP裝置I （Rotating Basket Apparatus），轉速100 rpm，測定10、20、30、45、60及90分鐘各時間點之溶離量，以繪製溶離曲線；並依照FDA所提SUPAC之f2 因子，與對照品比較其相似性。十六件檢體之溶離曲線與對照品比對結果，於三種溶媒之溶離曲線均與對照品相似者有五件（相似比率約31.3%），於水及0.1N HCl二溶媒中具相似性但於pH 7.4磷酸緩衝液不相似者有三件（約18.8%），而各只於單一溶媒，即0.1N HCl 或pH 7.4磷酸緩衝液，具相似性者各一件（各約6.3%），其餘六件（37.5%）於三種溶媒之溶離曲線均與對照品不相似。綜合16件檢體與原廠對照品之溶離曲線的相似性，分別為水中溶離相似者八件（50%），0.1N HCl溶離相似者九件（56.3%）及pH 7.4磷酸緩衝液溶離相似者六件（37.5%）。